title: Repeated measurements of endothelin-1 precursor peptides predict the outcome in community-acquired pneumonia.
abstract: OBJECTIVE
  Excessive activation of the endothelium is associated with adverse outcomes in patients with systemic infections. Endothelium-associated peptides, such as endothelin-1 (ET-1), correlate closely with endothelial activation, and therefore serve as surrogate biomarkers. Our aim was to investigate precursor peptides of endothelin-1 (proET1) on admission and during follow-up on days 3, 5 and 7 in a prospective cohort of 925 patients with community-acquired pneumonia.
  
  
  METHODS
  We investigated the association of initial and follow-up proET1 and other prohormone levels with 30-day mortality and ICU admission in proportional Cox regression models with time-varying covariates adjusted for the pneumonia-severity-index (PSI), and calculated reclassification statistics.
  
  
  RESULTS
  The mortality rate and ICU admission rate were 5.4% (95% CI 3.9-6.8%) and 9.0% (95% CI 7.1-10.8%). ProET1 levels on admission and changes from baseline to day 3 were significant mortality predictors with adjusted hazard ratios of 10.5 (95% CI 2.9-38.6) and 28.4 (95% CI 7.0-115.1). Initial proET1 levels improved the PSI in reclassification statistics (net reclassification improvement of 0.29, p<0.0001) and in c-statistics (from 0.79 to 0.83, p<0.01). Changes of proET1 on day 3 improved the c-statistic of the combined model of PSI and initial proET1 from 0.80 to 0.85 (p<0.01) and reclassification tables demonstrated a significant improvement (net reclassification improvement 0.44, p<0.0001). Similar significant results were found for the risk for ICU admission.
  
  
  CONCLUSIONS
  In community-acquired pneumonia, ET-1 precursor peptides on admission and changes from baseline to day 3 were independent predictors for mortality and ICU admission, and significantly improved the PSI. If verified in intervention studies, monitoring of proET1 may be helpful for endothelium targeting therapies and for risk stratification complementary to other prohormones.
authors.affiliation: Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Schuetzph@gmail.com
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
authors.forename: Werner
authors.initials: W
authors.lastname: Zimmerli
authors.forename: Beat
authors.initials: B
authors.lastname: Mueller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D017714:Community-Acquired Infections / Q000503:physiopathology*; D019332:Endothelin-1 / Q000097:blood* / Q000378:metabolism; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000503:physiopathology*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D013557:Switzerland / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D019332:Endothelin-1